Chrysanthemic acid esters



United States Patent 3,266,984 CYSANTHEMIC ACID ESTERS Kenzo Ueda,Nishinomiya-shi, Sadao Horie, Suita-shi, Toshio Mizutani, Ikeda-shi,Katsuji Nodera and Keimei Fujianoto, Minoo-shi, and Yositosi Okuno,Nishinomiya-shi, Japan, assignors to Sumitomo Chemicai Company, Ltd,Higashi-ku, Osaka, Japan, a corporation of Japan No Drawing. Filed Aug.4, 1965, Ser. No. 477,290 Claims priority, application Japan, Aug. 28,1964, 39/ 39,158; Aug. 29, 1964, 39/ 19,119; Sept. 15, 1964, 39/52,950,39/52,951

(Ilaims. (Cl. 16733) This invention relates to novel chrysanthemic acidesters, to a process for preparing the same, and to insecticidalcompositions containing the same. More particularly, it relates to novelchrysanthemic acid esters having the general formula:

wherein G represents a member selected from the group consisting of andwherein R is a member selected from the group consisting of hydrogenatom and lower alkyl radicals having 1 to 4 carbon atoms, and R and Reach represent a member selected from the group consisting of hydrogenatom and lower alkyl radicals having 1 to 2 carbon atoms; and Xrepresents a member selected from the group consisting of oxygen andsulfur atoms; to a process for preparing the same; and to insecticidalcompositions containing the same.

It is one object of the invention to provide a novel group ofchrysanthemic acid esters, which have strong insecticidal activities tohouse and agricultural insects with low toxicities to mammals andplants, and which can be commercially produced in low cost. Anotherobject is to provide a process for preparing such novel esters by acommercially available procedure. Still another object is to provideinsecticidal compositions containing such an ester. Other objects wouldbe obvious from the following description.

As an insecticide utilizable with safety because of the harmlessness tomammals, .pyrethrum extract has long been employed. Recently, allethrinwhich is an analogue of the effective ingredients in pyrethrum extract,i.e. pyrethrin and cinerin, was synthesized and developed forinsecticidal uses. These ingredients are certainly valuable in theirhigh insecticidal powers, especially in their rapid effect to insects,and in the characteristics of permitting no, or little, resistivity toinsects. However, their uses are limited to some extent because of theircomplicated steps of the production and their great expense for theproduction.

The present inventors have made broad researches on the variouschrysanthemic acid esters, and have now found the present novel group ofchrysanthemic acid esters, which possess significant insecticidal powerbut are 'ice harmless to mammals, and which can be prepared from easilyavailable materials by a simple process with low prices. In other words,the present compounds are thiazolidinomethyl esters of chrysanthemicacid. Accordingly, it is significant that the characteristics of thepresent compounds resemble pyrethrin, cinerin and allethrin, even thoughthe alcohol moieties of the former are extremely simple as com-pared tothose of the latter and are composed of carbon, hydrogen, oxygen,(sulfur) and nitrogen atoms, unlike the latter composed of carbon,hydrogen and oxygen.

Thus, the present invention is to provide novel chrysanthemic acidesters having the formula,

wherein G and X have the same meanings as identified above, and toprovide a process for preparing such compounds, comprising esterifying athiazolidine compound having the general formula,

0 II o wherein G and X have the same meanings as identified above, withchrysanthemic acid having the formula,

on, on,

according to the general esterifying procedure.

The thiazolidine compounds employed in the present invention, in otherwords, N-methylol-thiazolidines or 3- (hydroxymethyl)-thiazolidines, maybe prepared from the corresponding thiazolidine according to theprocedures well known to those skilled in the art. For instance, 3-(hydroxymethyl)-thiazolidine may be prepared by reaction of thiazolidinewith formaldehyde or its low molecular weight polymer according to theconventional methylolation conditions in the presence or absence of analkaline catalyst, such as sodium hydroxide and potassium carbonate, ina solvent, such as water, benzene, and toluene. Similarly, various3-(hydroxymethyl)-thiazolidines, as disclosed in the examples may beprepared.

The chrysanthemic acid employed in the present invention is the acidicmoieties of pyrethrin I, cinerin I and allethrin, and can be synthesizedaccording to the known method.

The esterification reaction of the present invention may be effected invarious ways. The thiazolidine compound may be heated with thechrysanthemic acid in the presence of a strong acid, such as aromaticsulfonic acid and sulfuric acid, in an organic solvent capable ofazeotropically boiling with water, thereby removing from the reactionsystem the water formed in the esterification. It may also be heatedwith a lower alkyl ester of the chrysanthemic acid in the presence of abasic catalyst, such as sodium, potassium, sodium alcoholate andpotassium alcoholate, thereby to continuously remove the lower alcoholformed through the trans-esterification reaction out of the reactionsystem. In such a case, methyl, ethyl, n-propyl and isopropyl ester aresuitable. In the most preferable esterification procedure, it may betreated with l idine was mixed with 0.03 mol of dry pyridine and 20 ml.of dry toluene. On the other hand, another solution was prepared bymixing 0.021 mol of chrysanthemoyl chloride and 10 ml. of dry toluene.When both the solutions were the chrysanthemic acid halide in an inertorganic solvent, 5 mixed at a temperature below 40 0, reaction startedpreferably in the presence of a dehydrohalogenating agent,exothermically and white crystal of pyridine hydrochlosuch as pyridine,triethylamine and other tertiary amine ride was separated. The reactionwas completed by allowwhereby the esterification proceeds with theisolation of ing the reaction mixture held in a tightly stoppered vessela hydrohalic acid salt within a short period of time. In to standovernight at room temperature. The mixture this case, the acid chlorideis the most preferable, though was then washed successively with 5%hydrochloric acid, the bromide and the iodide may be employed. Further,5% aqueous sodium carbonate solution and saturated soit may be refluxedwith the chrysanthemic acid anhydride dium chloride solution and driedover anhydrous magin an inert solvent for several hours, thereby toyield the nesium sulfate. Then the reaction mixture was purified esterrequired and free crysanthemic acid, the latter being by running downthrough a column packed with active recovered and again converted to theanhydride by treatalumina. After distilling oft toluene at a reducedpresment with, for example, acetic anhydride for reuse. Alsure andfurther driving off remaining toluene at a highly ternatively, thethiazolidine compound may be employed reduced pressure (0.01 mm. Hg)colorless or pale yelfor the esterification after being once convertedto the lowish viscous oily product was obtained. form of the halidehavngg the general formula, Method B which p y acid anhydride IL Zeropoint zero two mol of a 3-hydroxymethyl-thiazolidine was mixed with 0.02mol of chrysanthemic acid anhydride and 30 ml. of dry toluene andrefluxed for 3 2 hours. After cooled the mixture was treated with 5%aqueous solution of sodium carbonate to remove by-prof ducedchrysa-nthemic acid, washed with saturated aqueous X solution of sodiumchloride and dried over anhydrous wherein G and X have the Same meaningsas identifigd magnesium sulfate. Thereafter the similar treatment asabove, and A means a halogen atom In this Case, the in the method A wascarried out to obtam the product of halide may be heated with an alkalimetal or ammonium ester' salt of the crysanthemic acid in an inertsolvent, thereby Method C Whlch employs to yield the ester required withthe isolation of an alkali Zero point Zero two mol of a 3 chloromethylthiazol, metal or ammonium hahde Aherhahvely the hahde idine obtained byreacting 3-hydroxymethyl-thiazolidine may be heated with the free acidin an mert solvent m the with thionyl chloride or phosphor ltrxichlorideat room Presence of a dehydrehalegehahhg agent Such terhary temperatureand 0.02 mol of chrysanthemic acid were h 1h the formula A y be any ofehlonhe, dissolved in 40 m1. of dry acetone. Zero point zero two hhheand lodlhe among, Whleh the former A ar e two mol of triethylamine wasdropped to the mixture with preferable and e Praeheable' AS the alkahmetals stirring and the mixture was refluxed for 2 hours. Mean- Sedhhhand Potasshhh ar e Preferable 40 while triethylamine hydrochlorideseparated. After com- A 15 'h the ehhysahihemle acid emPr1SeS pletion ofthe reaction the mixture was cooled and solid various stereoisomers andoptical somers. It is needless matter was filtered off The filtrate WasConoentrated at to that'the acld t denvatlves thereof as a reducedpressure. The residue was dissolved in 30 ml. scribed here1n1nvolvethe1r somersof toluene, washed successively with 5% hydrochloric processof the lhvehheh deserlhed h more detah acid, 5% aqueous solution ofsodium carbonate and satuwith reference to the following examples, whlchare h W- rated aqueous solution of sodium chloride and dried over everhe eehstrhed for the Purpose of lhhstratlon and anhydrous magnesiumsulfate. Thereafter the similar not of hhhtahoh' treatment as in themethod A was carried out to obtain EXAMPLES the product of ester.

5 The results of experiments carried out in accordance Method A whlchemploys acid chloride 0 with the above-mentioned general procedure areshown Zero point zero two mol of a 3-hydroxymethyl-thiazolin thefollowing Tables I and II.

TABLE I CH3 CH;

C CH3 Ex- Resultant ester RCHzO( iC CH CH=C/ arn- B-hydroxymethylEsterifiple thiazolidines used cation R CH3 No. method Elementaryanalysis Molecular Refractive Yield formula index 1 S-hydroxymethyl- ACHz-CO CuHmNOaSn 1111 15710 75% id"-.. 53. 98 6.45 4. 09 19.97rhodanine. N cald... 53.67 6.07 4.47 20. 45

S-C s 2 3-hydroxyn1ethyl- A CHaCHCO CuHzrNOsSz 1111 15447 fd 55.60 6.733.91 19.20 fi-methylrhodanine. N eald... 55.05 6.42 4. 28 19.57

See footnote at end of table.

'1 A BLE II-Continued if C H: R esultant ester RCH O- O- CE;C H- C H=CEx- C C Ha am- 3-hyd roxymethyl Esterifi ple thiazolidines used cation RC H: CH: No. method Elementary analysis Molecular Refractive Yieldformula index l 3 hydroxymethyl-5- A CHsCH=C-C O CmI-InNOaSz HD 1. 584075% id... 56. 97 6. 50 3.99 18.49 ethylidene-2-thio-4- caltl-.. 56. 646. 19 4. 13 18. 88 oxothiazolidine. /N

S C S l6 3-hydroxymethyl-5- B CaII5CH CC O C17H23NO3S2 7;1. 5792 70% fd58. 02 6.72 3. 73 17. 67 propylidene-Z-thiocald 57. 79 6. 52 3. 97 18.134-oxothiazolidine. /N

S C S 17 3-l1ydroxymethyk5- A (CH3) 2C=G C O C H NO-lS m l. 5339 86% id.601 62 7. 02 3. 97 9. 22 isopropylidene-2A- cald 60. 53 6. 82 4.15 9. 50dioxothiazolidinc. i N

S C O 18 3-hydroxymethyl-5- A CH3 CisHzsN 04S 711, 1. 5304 82% id... 61.89 7. 51 3. 73 8. 80 (1-methyl-propylicald 61. 54 7. 12 3. 99 9. 12dene) 2,4-di0xo- C=C- C O thiazolidine. t

C 2H5 I /N- S C O 19-" 3-hydroxymethyl-5- C (CaI I5)zC:CC O C1QH NO4S9%1. 5263 71% Id 62. 90 7. 69 3. 51 8.41 (l-methyl-propylicald 62. 47 7.3. 84 8. 77 done) -2,4-dioxo- N thiazolidine (used after chlorinated). SC O 20-" 3-hydroxymethyl-5- A CHaCH C-C O OIUH21N04S 711, 1. 5294 77% fd59. 93 6.92 3.98 9. 72 ethylideneQA- l 031d. 59. 44 6. 4. 33 9. 91dioxothiazolidine. /N

S C O 21.-. 3-hyd1'oXymethyl-5- A C2H5CH:CC O C17H23NO4S 111, 1. 524775% fd 60. 92 7.12 3. 81 9.18 normal propylidene I cald... 60. 53 6. 824. 15 9. 50 2,4-dioxothiazoli- N- dine.

Note: id. =found, cald. =calculatcd.)

As mentioned above, the present esters possess superior insecticidalpower, and exhibit rapid knock down and excellent killing effect on e.g.houseflies, mosquitos, cockroaches. Moreover, these esters areespecially useful for sanitary and domestic purposes, because of theirrapid effectiveness and harmlessness. The present esters are suitablyemployed for the preparation of insecticidal compositions which havebroad uses, correlative-1y with the low cost.

For the formulation of the insecticidal composition containing thepresent compound as the essential ingredient, oil solution, emulsifiableconcentrate, wettable powder, dust, aerosol, mosquito coil (a burningincense device for warding oif mosquitoes), bait and other preparation,may be formulated using generally employed carriers, diluents orauxiliary agents, according to the method known to those skilled in theart in the cases of the formulation of pyrethrum extract and allethrin.

If desired, the present esters may be employed for the preparation ofthe insecticidal compositions in combination with another insecticidalcomponent, such as pyrethroide, for example, pyrethmm extract andallethrin, organochlorine and organophosphorus compounds, synergisticagent for pyrethroide, for example, piperonyl butoxide, piperonyl sulfoxide, fi-butoxy-fl thiocyanodiethyl ether and the like. By combinationwith such other ing-redient, the present insecticidal composition can beadapted to broader uses with increased effect.

The present esters may be blended with at least one of pyrethrin,allet-hrin, 0,0-dimethyl-O-(3-methyl-4-nitrophenyl) thiophosphate,Malathion, trademark, diazinone, dimethoate, 'y-BHC, and others, toyield a pestici- (1) OH (|)H containing 1 O 0 H3 0 CH (CI'Ia);C C(CH3);

OH 011 (CHa)zC-CH2- jC(CH i on, on,

( OH OH CH 1 CH3 H w I I CH3 CH3 The amount of the stabilizer, if added,may be less than 1% by weight of the present ester, ordinarily from 1 to0.1%.

The fol-lowing are examples are insecticidal compositions containing thecyclopropanecarboxylic acid esters according to the invention and of theinsecticidal activities. Parts are by weight.

EXAMPLES A compound of the present invention shown below is made into anoil preparation using refined kerosene (in cases of some compounds, asmall amount of Xylene is added thereto). With use of a turn-tableapparatus of Campbell (Campbell, F. L., Sullivan, W. N., Soap and PaintChemicals, vol. 14, No. 6, p. 119, 1938) ml. of the oil preparation issprayed within seconds. After seconds, the shutter is opened and housefly adults (one group of about 100) are exposed to the sprayed mist for10 minutes. Then the houseflies are transferred to an observation cageand the knock down numbers at that time and mortalities after 24 hoursare calculated.

TABLE III Concentration Knock down Mortality after Example No. ofefiective ratio after 10 24 hours ingredient minutes (per- (percent)(percent) cent) 1. 0 About 90 65. 3

1. 0 About 90 61. 6

1. 0 About 80 52. 2

1. 0 About 80 55. 7

In the above table the effective ingredient is as follows:

(22) CH2CO OH:

N-CH20-CCHCH-CH=O/ i CH3 SCS CH1 CH 3-ch1'ysantheomoxymethylrhodanineCH: N-CHO-C-CHCH-CH=C 22 CHaCHC o (24) CzH5CH C 0 S -CS CH3 CH3d-chrysttnthemoxymethyl-S-ethylrho(ilanine C Hs C Ha3-chrysanthemoxymethyl 5-propylrhodanine i-CaHi-C HC O SOO 0 H C H3-chrysanthemoxymethyl-5-ethyl-2,4-dioxothlazolidine i-C3H7CHCO CH3 N-OH2O O -CHCH-CH=C S -C O H C H CH: CH:

3-chrysanthemoxymethyl-5-is0propyl-2A-d1oxothiazolidine H'C4HQCH CO /CH/N-CHzO-C-CHCH'CH=C SCO 0 CH CH CH3-chrysanthemoxymethyl-5-butyI-2,4-dloxothiazolidine C: CO CH; CH N-CHO'("3-Cg/CH-CH=C S-C S O O CHa CH C H3-chrysanthem0xymethyl-5-1sopropy1idene2-thlo-4- oxothiuzolidine3-chrysanthemoxymethyI-S-(l-methyl-normal propylidene)-3-c11rysanthemoxymethy1-5-(l-ethyl propyidene)-2-thto-4-2-thto-4-0xothlazo1idine oxothiazolidine3-chrysanthernoxymethyl-5-ethylidene-2thio-4-oxothiazolidine3-cl1rysanthemoxymethyl-5-(1-methyl normal propylidene)2,4-dioxothiazolidine CH3 on 3-chrysanthemoxymethyl-5- (l-ethyl normalpropy1idene)- 2,4-dixothiazolidine CH1'CH=C-CO /CII N-OHzO-C-CH-ClI-CH=CS-CO 0 CH CH CH 3-chrysanthemoXymethyl-5-ethylidene-2,4-

dioxothiazolidine (42) CzH5-CH=CCO CH S-CO C- CH CH CH 3cl1rysanthemoxymethyl5-pr0pylidene-2,4- dioxothiazolidine Example 43 Tenparts of 3chrysanthemoxymethylrhodanine, parts of Sorpol SM-ZOO (a tradename of a surfactant manufactured by Toho Chemical Co., Ltd.), and 80parts of xylene were mixed in this order and dissolved with stirring toproduce an emulsifiable concentrate.

Housefly adults (one group of about 50) were liberated in a high Petridish, which was then closed with a metal net lid and charged to thebottom of a settling tower. Ten ml. of the solution of theabove-mentioned oil preparation diluted 10 times with water was sprayedupward by a pressure of lb. per sq. in. After 20 seconds, the shutterwas opened and the houseflies were exposed to the descending mist for 10minutes, taken out and placed in a room kept at a temperature of 27 C.The mortality was 80.5 percent after 20 hours.

Example 44 Two parts of 3chrysanthemoxymethyl-S-methylrhodanine wasdissolved in 20 parts of acetone and 98 parts of 200 mesh talc wereadded thereto. After sufiiciently stirred and mixed in a mortar, themixture was freed from acetone by evaporation to produce dust.

Housefiy adults (one group of about 50) were liberated in a high Petridish, which was then closed with a metal net lid and charged to thebottom of a settling tower. One gram of the above-mentioned dust wasscattered upward by a pressure of 20 lb. per sq. in. After 10 seconds,the shutter was opened and the houseflies were exposed to the descendingpowder for 10 minutes, taken out and in a room kept at a temperature of27 C. The mortality was 97.6 percent after 20 hours.

Example 45 One point five g. of 3chrysanthemoxymethyl-Smethyl-2,4-dioxothiazolidine was dissolved in 30 ml. of acetone and thesolution was stirred and mixed with 98.5 g. of a mosquito coil carrier(a blend of tabu powder and pyrethrurn marc in 2:3 proportion byweight). After evaporating acetone, ml. of water was added to themixture and the mixture was kneaded. Sufliciently kneaded mixture wasmolded and dried whereby mosquito coil containing 1.5 percent ofeifective ingredient was obtained.

About 30 northern house mosquitoes (adult) were liberated in a 70 cm.glass box, one g. of the abovementioned mosquito coil was heldhorizontally on a mosquito coil holder placed in the center of bottom ofthe box, both ends of the mosquito coil were ignited and the knock downnumber of the mosquitoes was counted. The result is as follows:

KNOCK DOWN RATIO OF NORTHERN HOUSE MOSQUITOES RELATIVE TO ELAPSE OF TIME(PERCENT) I 3min. 6 min. 12 min. 24 min. 48 min.

The mosquito coil containing 1.5 percent of the composition of thepresent invention 15. 1 49. 4 93. 4 96. 9

Example 46 KNOCK DOWN RATIO OF HOUSEFLIES RELATIVE TO ELAPSE OF TIME(PERCENT) 30 see. 1 min. 2 min. 4 min. 8min. 11 min.

20 sec.

The composition of the present invention 0 3. 9 25. 4 43. 9 59. 7 78. 5An oil preparation containing 3% allethrin 0 7. 7 24. 9 53. 6 65. 1 76.7

Example 47 In similar way as described in Example 43, a 10% emulsifiableconcentrate containing3-chrysanthemoxymethyl-5-isopropylidene-2-thio-4oxothiazolidine wasprepared and tested. Mortality after 20 hours was 88.0%.

Example 48 In similar Way as described in Example 44, a 2% dustpreparation containing3chrysanthemoxymethyl-S-ethylidene-2-thio-4-oxothiazolidine was preparedand tested. Mortality after 20 hours was 90.6%.

13 Example 49 In similar way as described in Example 46, a 0.3% oilpreparation containing3-chrysanthemoxymethyl-S-isopropylidene-2,4-dioxothiazolidine wasprepared and tested. The result is shown as follows:

KNOCK DOWN RATIO OF HOUSEFLIES ACCORDING TO THE LAISE OF TIME (PERCENT)Example 50 In similar way as described in Example 45, a 1.5% mosquitocoil containing3-chrysanthemoxymethyl-S-isopropylidene-2,4-dioxothiazolidine wasprepared and tested.

KNOCK DOWN RATIO OF NORTHERN HOUSE MOSQUI TOES RELATIVE TO ELAPSE OFTIME (PERCENT) 3 min. 6 min. 12 min. 24 min.

The mosquito coil of the present invention 4. 3 l8. 7 63. 8 94. 8

Example 51 0.4 part of 3-chrysanthemoxymethyl-5-(l-methyl-normalpropylidene)-2,4-dioxothiazolidine, 2 parts of piperonyl butoxide, 6.3parts of xylene and 6.3 parts of refined kerosene were mixed and chargedto an aerosol vessel. After fixing a valve part, 85 parts of ejectingagent (e.g. Freon, monomeric vinyl chloride, liquefied petroleum gas orthe like) Were charged by a pressure to produce aerosol.

About 30 houseflies (adult) were liberated in a 70 cm? glass box, theabove-mentioned aerosol was sprayed in the space of the box for onesecond (the amount of the active ingredient was about 0.6 g.) and theknock down number of the houseflies was counted. The result is asfollows:

KNOCK DOWN RATIO OF HOUSEFLIES RELATIVE TO ELAPSE OF TIME (PERCENT) WhatWe claim is: 1. A chrysanthemic acid ester having the formula,

wherein G represents a member selected from the group consisting of andwherein R is a member selected from the gr up consisting of hydrogenatom and lower alkyl having 1 to 4 carbon atoms, and R and R eachrepresent a member selected from the group consisting of hydrogen atomand lower alkyl having 1 to 2 carbon atoms; and X represents a memberselected from the group consisting of "oxygen and sulfur atoms.

2. An insecticidal composition containing a chrysanthemic acid ester asdefined in claim 1, as the essential active ingredient and an inertcarrier.

3. An insecticidal oil solution containing a chrysanthemic acid ester asdefined in claim 1, as the essential active ingredient and an inertsolvent.

4. An insecticidal emulsifable concentrate containing a chrysanthemicacid ester as defined in claim 1, as the essential active ingredient, adispersing agent, and an inert solvent.

5. An insecticidal dust preparation containing a chrysanthemic acidaster as defined in claim 1, as the essential active ingredient, and apowdered carrier.

6. An insecticidal wettable powder containing a chrysanthemic acid esteras defined in claim 1, as the essential active ingredient, a dispersingagent and a powdered carrier.

7. An insecticidal aerosol containing a chrysanthemic acid ester asdefined in claim 1, as the essential active ingredient and propellant.

8. A mosquito coil containing a chrysanthemic acid ester as defined inclaim 1, as the essential active ingredient and a mosquito coil carrier.

9. An insecticidal bait preparation containing a chrysanthemic acidester as defined in claim 1, as the essential active ingredient, andfood materials for insects.

10. A method for killing insects, which comprises treating the insectswith a toxic amount of a chrysanthemic acid ester having the formula,

wherein G represents a member selected from the group consisting ofwherein R is a member selected from the group consisting of hydrogenatom and lower alkyl having 1 to 4 5 carbon atoms, and R and R eachrepresent a member selected from the group consisting of hydrogen atomand lower alkyl having 1 to 2 carbon atoms; and X represents a memberselected from the group consisting of oxygen and sulfur atoms.

No references cited.

JULIAN S. LEVITT, Primary Examiner.

STANLEY I. FRIEDMAN, Assistant Examiner.

10. A METHOD FOR KILLING INSECTS, WHICH COMPRISES TREATING THE INSECTSWITH A TOXIC AMOUNT OF A CHRYSANTHEMIC ACID ESTER HAVING THE FORMULA,